Detection of colonic mucosal phosphorylated α⁃synuclein in patients with Parkinson’s disease and its clinical significance
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摘要:
目的：探讨磷酸化α-突触核蛋白（phosphorylated α-synuclein，pSNCA）在帕金森病便秘（PD patients with constipation，PDC）患者结肠黏膜中的表达及其与非运动症状的关系。方法：将10例PDC患者及10例性别、年龄匹配的功能性便秘（functional constipation，FC）患者纳入研究，进行临床资料及非运动症状的评估。通过内镜活检获取每位受试者升、降结肠黏膜组织各2块，用免疫组织化学技术染色并评估pSNCA和神经元标志物-神经丝蛋白（NF）的表达，并进行共定位。最后进行pSNCA与非运动症状之间的相关性分析以探索非运动症状的发生机制。结果：所有PDC患者结肠黏膜均表达pSNCA（10/10），对照组阳性率90%（9/10），两组阳性率差异无统计学意义；但两组pSNCA的表达量差异有统计学意义（P＜0.05），且PDC组更为显著；PDC患者的pSNCA表达量与H-Y分期存在相关性（r=-0.59，P＜0.05），而与病程、UPDRS Ⅲ评分、LEDD无关，便秘严重程度与UPDRS Ⅲ评分存在相关性（r=0.67，P＜0.05）。此外，患者非运动症状（包括焦虑、抑郁、睡眠障碍、疲劳、便秘）的严重程度与肠道pSNCA的沉积无关。结论：pSNCA的沉积可能参与便秘以及帕金森病的发生发展，但与帕金森病的非运动症状无关。
Abstract:
Objective：To investigate the expression of phosphorylated α-synuclein（pSNCA）in colonic mucosa of Parkinson's disease（PD）patients with constipation and its relationship with non-motor symptoms. Methods：Ten constipated patients with PD（PDC）and 10 gender- and age-matched patients with functional constipation（FC）were enrolled in this study，and the clinical data and non-motor symptoms were evaluated. Two specimens of ascending and descending colonic mucosa were obtained from each subject by endoscopic biopsy. pSNCA and neurofilament protein（NF）were stained by immunohistochemistry and colocalized. Finally，the correlation between pSNCA and non-motor symptoms was conducted to explore the mechanism of non-motor symptoms in PD. Results：All PDC patients displayed pSNCA（10/10）in the colonic mucosa and 90%（9/10）in the control group，with no significant difference between the two groups. However，there was a statistically significant difference between the two groups in the expression of pSNCA（P＜0.05），and the PDC group was more significant. The level of pSNCA in PDC patients was related to H-Y stage（r=-0.59，P＜0.05），but not with disease duration，UPDRS-Ⅲ score and LEDD. The severity of constipation in PD was associated with UPDRS-Ⅲscore（r=0.67，P＜0.05）. In addition，the severity of non-motor symptoms（including anxiety，depression，sleep disturbances，fatigue，constipation）in patients was not related to the deposition of pSNCA in the intestine. Conclusion：The deposition of pSNCA may be involved in the development of constipation and Parkinson’s disease，but not corelate with the non-motor symptoms of Parkinson’s disease.
